AK155 is a cytokine that is structurally related to interleukin-10 (IL-10). A number of cytokines have been classed as IL-10-like, based on their structure. The IL-10-like cytokines include IL-20, IL-22, and mda-7, as well as AK155 (Moore, et al. (2001) Annu. Rev. Immunol. 19:683–765; Moore, et al. (1993) Annu. Rev. Immunol. 11:165–190). Cytokines are signaling molecules that mediate communication between cells, e.g., between cells of the immune system. Once secreted, cytokines travel to a different or identical cell, bind to a membrane-bound receptor, and provoke a series of events such as protein phosphorylation or gene activation, where these events result in changes in phagocytic or secretory activity, or changes in migration, differentiation state, and proliferation activity.
The cytokines may be classed into those associated with increased inflammation (Th1-type response) and decreased inflammation (Th2-type response). The Th1-type response is characterized by increases in production of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), TNF-β, IL-12, IL-18, and other pro-inflammatory cytokines (Sallusto, et al. (1998) Immunol. Today 19:568–574). IL-17 is generally a pro-inflammatory cytokine (Fort, et al. (2001) J. Immunol. 15:985–995). Th2-type response is characterized by increases in production of cytokines that suppress inflammation, e.g., IL4, IL-5, IL-10, and IL-13 (Liu, et al. (2001) Nature Immunol. 2:585–589). IL-25 appears to suppress inflammation (Fort, et al. (2001) J. Immunol. 15:985–995).
Within one interleukin family, such as the IL-1 family, different interleukins may be functionally related to each other in that they influence the course of one event, but exert opposite effects on that event. For example, IL-1ε has a pro-inflammatory effect, while IL-1δ has an anti-inflammatory effect (Debets, et al. (2001) J. Immunol. 167:1440–1446). IL-17 and IL-25 are examples of two other cytokines which are structurally similar, but produce opposite biological effects. The structure of any particular cytokine therefore serves as a guide to determining its physiological function.
An analysis of cell signaling proteins can also help determine a cytokine's role in physiology. For example, signaling involving signal transducers and activators of transcription-4 (STAT4) may indicate an inflammatory response, while signaling via STAT6 may indicate an anti-inflammatory response or Th2-type response (Romagnani (1997) Immunol. Today 18:263–266). Hence, the identities of the proteins that are phosphorylated, of the particular amino acid residues that become phosphorylated, and of the relevant transcription factors and genes that become activated, are all relevant to determining the function of the cytokine of interest. Other powerful techniques for determining the functions of cytokines and related signaling proteins include use of genetically altered animals where a specific gene is altered in all cells, e.g., IL-10−/− mice (Scheerens, et al. (2001) Eur. J. Immunol. 31:1465–1474), or where the genetic alteration is targeted to only one type of cell in the animal, e.g., liver cells, epithelial cells, cells of lymphoid lineage (Blumberg, et al. (2001) Cell 104:9–19), or macrophages and neutrophils (Takeda, et al. (1999) Immunity 10:39–49).